Cellular Changes in Retinas From Patients With BEST1 Mutations

Vera L Bonilha; Brent A Bell; Meghan J DeBenedictis; Stephanie A Hagstrom; Gerald A Fishman; Joe G Hollyfield

doi:10.3389/fcell.2020.573330

Cellular Changes in Retinas From Patients With BEST1 Mutations

Front Cell Dev Biol. 2020 Oct 14:8:573330. doi: 10.3389/fcell.2020.573330. eCollection 2020.

Authors

Vera L Bonilha^{1

2}, Brent A Bell^{1

3}, Meghan J DeBenedictis¹, Stephanie A Hagstrom^{1

2}, Gerald A Fishman⁴, Joe G Hollyfield^{1

2}

Affiliations

¹ Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States.
² Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, United States.
³ Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, United States.
⁴ Pangere Center at The Chicago Lighthouse for People Who Are Blind or Visually Impaired, Chicago, IL, United States.

Abstract

Best disease (BD), also known as vitelliform macular dystrophy, is an inherited disease of the central retina caused by more than 300 pathogenic variants in the BEST1 gene. The phenotype of BD is variable, and there are just a few reports on the histopathology of eyes from donors with BD. Here, we describe the histopathological comparison of donor's eyes from two patients with BD. Eyes obtained from 85-year-old (donor 1) and 65-year-old (donor 2) donors were fixed within 25 h postmortem. Perifoveal and peripheral retinal regions were processed for histology and immunocytochemistry using retinal-specific and retinal pigment epithelium (RPE)-specific antibodies. Three age-matched normal eyes were used as controls. DNA was obtained from donor blood samples. Sequence analysis of the entire BEST1 coding region was performed and identified a c.886A > C (p.Asn296His) variant in donor 1 and a c.602T > C (p.Ile201Thr) variant in donor 2; both mutations were heterozygous. Fundus examination showed that donor 1 displayed a macular lesion with considerable scarring while donor 2 displayed close to normal macular morphology. Our studies of histology and molecular pathology in the perifovea and periphery of these two BD donor eyes revealed panretinal abnormalities in both photoreceptors and RPE cellular levels in the periphery; donor 1 also displayed macular lesion. Our findings confirm the phenotypic variability of BD associated with BEST1 variants.

Keywords: BEST1 gene; best disease; histopathology; photoreceptors; retinal pigment epithelium.

Abstract

Grants and funding